Relationship between donor-specific HPA-15 antibodies and poor graft function in HPA-15 mismatched cord blood transplantation
Relationship between donor-specific HPA-15 antibodies and poor graft function in HPA-15 mismatched cord blood transplantation
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HPA-15错配脐带血移植中供者特异性HPA-15抗体与移植物功能不良的关系
DOI：
10.1007/s12185-022-03286-z
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发表时间：
2022
影响因子：
2.1
通讯作者：
Karasuno Takahiro
中科院分区：
文献类型：
--
作者：
Yasumi Masato;Yokota Takafumi;Endo Takaya;Kusakabe Shinsuke;Koh Yangsook;Sakamoto Hiroe;Inoue Hiroko;Sudo Takao;Hosen Naoki;Karasuno Takahiro
移植物功能低下(PGF)是造血干细胞移植后的致命并发症，受多种因素的影响，如供者特有的抗人类白细胞抗原抗体、CD34+细胞输注不足和供者来源。抗人血小板抗原15(HPA-15)的同种异体抗体识别血小板膜糖蛋白CD109，CD109不仅在血小板上表达，而且在巨核细胞和特异的造血干细胞上也有表达。已知HPA-15抗体可导致血小板输注困难和新生儿同种免疫性血小板减少，但它们对造血干细胞移植后移植物功能的影响尚不清楚。我们遇到了一例HPA-15b抗体滴度较高的HPA-15不合脐血移植病例。持续高滴度HPA-15b抗体阳性的PGF延长和巨核细胞再生障碍性贫血经利妥昔单抗治疗后得到缓解，并可迅速恢复造血功能。HPA-15相合的血小板输注对血小板恢复非常有效。甲基纤维素分析和巨核细胞培养显示，患者血清在体外抑制患者骨髓细胞的造血细胞发育。这些结果提示HPA-15抗体可能是PGF的原因之一，降低HPA-15抗体效价可能会改善HPA-15不相合移植的移植物功能。
Poor graft function (PGF) is a fatal complication following hematopoietic stem cell transplantation and is influenced by multiple factors, such as donor-specific anti-HLA antibodies, a poor infused CD34+cell count, and the donor source. Alloantibodies against human platelet antigen 15 (HPA-15) recognize platelet membrane glycoprotein CD109, which is expressed not only on platelets, but also on megakaryocytes and specific hematopoietic stem cells. HPA-15 antibodies are known to induce platelet transfusion refractoriness and neonatal alloimmune thrombocytopenia, but their effects on graft function following hematopoietic stem cell transplantation remain unknown. We encountered a case of HPA-15 mismatched cord blood transplantation with a high HPA-15b antibody titer. Prolonged PGF and megakaryocyte aplasia with sustained high-titer HPA-15b antibodies were attenuated by rituximab therapy, and rapid recovery of hematopoiesis was achieved. HPA-15-compatible platelet transfusions were highly effective for platelet recovery. Methylcellulose assays and megakaryocyte cultures revealed that patient serum inhibited in vitro hematopoietic development from patient bone marrow cells. These results suggest that HPA-15 antibodies might be a cause of PGF and that reducing the HPA-15 antibody titer might improve graft function in HPA-15 mismatched transplantation.
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